4-chloro-7-(4-pyridyl)-3-quinolinecarboxylates

ABSTRACT

Lower-alkyl 4-Q-7-(Q&#39;&#39;-4-pyridyl)-3-quinoline-carboxylate (I) where Q is halo or lower-alkoxy, and Q&#39;&#39; is hydrogen or from one to two lower-alkyl groups, is prepared by reacting lower-alkyl 1,4-dihydro-4-oxo-7-(Q&#39;&#39;-4-pyridyl)-3-quinolinecarboxylate (II) with a halogenating agent to produce said compound (Ia) where Q is halo and then reacting the resulting 4-halo compound with alkali metal lower-alkoxide to produce said compound (Ib) where Q is lower-alkoxy. The lower-alkyl 4-(lower-alkoxy)-7-(Q&#39;&#39;-4pyridyl)-3-quinolinecarboxylate (Ib) is hydrolyzed under acidic conditions to produce lower-alkyl 1,4-dihydro-4-oxo-7-(Q&#39;&#39;-4pyridyl)-3-quinolinecarboxylate (II), which is useful as an intermediate in the preparation of lower-alkyl 1-(lower-alkyl)1,4-dihydro-4-oxo-7-(Q&#39;&#39;-4-pyridyl)-3-quinolinecarboxylate and -3quinolinecarboxylic acid, antibacterial agents.

United States Patent 1191 Lorenz et al.

[ 5] Jan. 21, 1975 [5 4-ClILORO-7-(4-PYRIDYL)-3- QUINOLINECARBOXYLATES [75] Inventors: Roman R. Lorenz, East Greenbush;

, R. Pauline Brundage, Schodack,

211 Appl. No.: 418,189

Related US. Application Data [62] Division of Ser. No. 263,787, June 19, 1972, Pat. No.

[52] US. Cl. 260/287 R, 260/295 R, 424/258 [51] Int. Cl C07d 33/48 [58] Field of Search 260/287 R [56] References Cited UNITED STATES PATENTS 3,287,458 11/1966 Kaminsky 260/287 3,324,135 6/1967 Lesher 260/287 3,397,208 8/1968 Berman 260/287 3,472,859 10/1969 Lesher 260/287 3,496,184 2/1970 Mizzoni 260/287 R 3,506,667 4/1970 Kaminsky 260/287 R 3,563,981 2/1971 Lesher 260/287 FOREIGN PATENTS OR APPLICATIONS 1.207.771 10 1970 Great Britain 260/287 Primary ExaminerDonald G. Daus Assistant Examiner-D. Wheeler Attorney, Agent, or Firm-Robert K. Bair; B. Woodrow Wyatt [57] ABSTRACT Lower-alkyl 4-O-7-(()'-4-pyridy1)-3-quin0linecarboxylate (l) where Q is halo or lower-alkoxy. and Q is hydrogen or from one to two lower-alkyl groups. is prepared by reacting lower-alkyl 1.4-dihydro-4-oxo- 7-(O'-4-pyridyl)-3-quinolinecarboxylate (11) with a halogenating agent to produce said compound (la) where Q is halo and then reacting the resulting 4-halo compound with alkali metal lowcr-alkoxide to produce said compound (lb) where Q is lower-alkoxy. The lower-alkyl 4-(lower-a1koxy)-7-(Q'-4-pyridyl)-3- quinolinecarboxylate (lb) is hydrolyzed under acidic conditions to produce lower-alkyl 1,4-dihydro-4-oxo- 7-(Q'-4-pyridyl)-3-quinolinecarboxylate (II), which is useful as an intermediate in the preparation of loweralkyl 1-(lower-alkyl)-l ,4-dihydro-4-oxo-7-(Q'-4- pyridyl)-3-quinolinecarboxy1ate and -3- quinolinecarboxylic acid, antibacterial agents,

3 Claims, No Drawings 1 4-CHLORO-7-(4-PYRIDYL)-3- QUINOLINECARBOXYLATES where Q is halo or lower-alkoxy, R is lower-alkyl, and Q is hydrogen or from one to two lower-alkyl groups. These compounds are useful as intermediates in the preparation ofthe corresponding lower-alkyl l-(loweralkyl )-1 ,4-dihydro-4-oxo-7-(Q'-4-pyridyl )-3- quinolinecarboxylates and -3-quinolinecarboxylic acids. which are useful as antibacterial agents and which are disclosed and claimed in the copending Lesher and Carabateas U.S. Patent application Ser. No. 144,307, filed May l7, l97l now U.S. Pat. No. 3,753,993. Preferred embodiments of the invention because of their relative ease of preparation from readily available and low costing intermediates are the compounds of Formula I where Q is hydrogen. methyl or ethyl. Q is methoxy or ethoxy, and R is methyl or ethyl.

The invention in a process aspect resides in the pro- MOR' 2 cess of reacting lower-alkyl 4-oxo-7-(Q-4-pyridyl)-3- quinolinecarboxylate of the Formula II l where R and Q are defined as hereinabove with a halolgenating agent to produce the compounds of Formula 5] where Q is halo.

l The invention in another process aspect resides in the process of reacting the compound of Formula I where :Q is halo and R is lower-alkyl with alkali metal lower- ;alkoxide, preferably using lower-alkanol as solvent, to

produce the compound of Formula I where Q is loweralkoxy. These 4-(lower-alkoxy) compounds also were isolated as by-products in yields of about 1010 35% in the reaction of lower-alkyl l,4-dihydro-4-oxo-7-(Q-4- pyridyll-3-quinolinecarboxylate of Formula H with an alkylating agent to produce the corresponding loweralkyl l-(lower-alkyl )-l ,4-dihydro-4-oxo-7-(Q-4- pyridyl)-3-quinolinecarboxylate.

The invention in another process aspect resides in hydrolyzing under acidic conditions the 4-(lower-alkoxy) compound of Formula I where Q islower-alkoxy to produce said lower-alkyl l,4-dihydro-4-oxo-7-(Q-4- pyridyl)-3-quinolinecarboxylate of Formula H, which, as noted above, on l-alkylation yields the antibacterially active lower-alkyl l-(lower-alkyl)-l,4-dihydro-4- oxo-7-(Q-4-pyridyl)-3-quinolinecarboxylates.

The processes of the invention are illustrated by the following flow sheet:

I 000R n where R and R are each lower-alkyl and can be the The manner and process of making and using the insame or different, Q s ydrogen or from one to two stant invention will now be generally described so as to lower-alkyl groups, and M is alkali metal. When the reenable a person skilled in the art of chemistry to make action of la with MOR is carried out using solvent and use the same as follows. lowcr-alkun l, R" H h r R" i rlkyl, the 5 The reaction which comprises reacting lower-alkyl sults are as follows l,4-dihydro-4-oxo-7-(Q-4-pyridyl)-3- 000R" MOR' Ia.

R"OH

where R and R" can be the same or different. Thus, quinolinecarboxylate (ll) with halogenating agent to MOR first reacts with R"OH to produce MOR which produce the corresponding lower-alkyl 4-halo-7-(Q-4- reacts with the 4-halo compound and the ester expyridyl)-3-quinolinecarboxylate (l, O is halo) is carried change reaction between R"OH and the 3-COOR com- 2( out by heating the reactants together in the absence or pound to produce the 3-COOR compound also takes presence of a suitable solvent at about 40 to 150C, place. preferably from about 80 to 120C. The reaction is The term lower-alkyl, as used herein, means alkyl conveniently run by heating only the reactants with groups having from one to six carbon atoms, illustrated stirring on a steam bath. While the preferred halogenatby methyl, ethyl, n-propyl, isopropyl, Z-butyl, isobutyl, ing agent is phosphorus oxychloride, other halogenatn amyl. n-hexyl, and the like, preferred groups because ing agents can be used, e.g., phosphorus oxybromide, of their ready'availability from low costing compounds phosphorus trichloride, phosphorus pentachloride, thibeing methyl and ethyl. onyl chloride, phenyl phosphonic dichloride, phosgene,

The term halo, as used herein, means chloro or and the like. Suitable solvents, if desired, include chlobromo, with chloro being preferred because of the roform, benzene, toluene, xylene, chlorobenzene,

ready availability and cost advantages of chloro intermethylene dichloride, and the like.

mediates. The reaction which comprises reacting lower-alkyl The term lower-alkoxy, as used herein, means alk- 4-halo-7-(Q'-4-pyridyl)-3-quinolinecarboxylate (l, O is oxy groups having from oneto six carbon atoms, illushalo) with alkali metal lower-alkoxide is carried out trated by methoxy, ethoxy, n-propoxy, isopropoxy, npreferably at about room temperature (about 25C.) or butoxy, 2-butoxy, isobutoxy, n-amoxy, n-hexoxy, and up to about 809C. and preferably using lower-alkanol the like. as solvent. Alternatively, lower temperatures, as low as The intermediate compounds illustrated by Formula about 0C., can be used although the completion of rell, exist in tautomeric forms, that is, as the l,4-dihydroaction might take longer. At least one molar equivalent 3-(COOR)-4-oxo-7-PY-quinolines of Formula [I andquantity of the alkalimetal lower-alkoxide is used per /or the 3-(COOR)-4-hydroxy-7-PY-quinolines of Formole of lower-alkyl 4-halo-7-(Q'-4-pyridyl)-3- mula ll, illustrated as follows: quinolinecarboxylate. Said alkali metal lower-alkoxide O OH I CQOR I COOR PY N PY N where R is lower-alkyl and PY is Q-4-pyridyl wherein can be generated by any of several well known proce- Q is hydrogen or from one to two lower-alkyl groups. dures, such as the reaction of an alkali metal or of any Measurements of the infrared spectra, in potassium alkali organometallic, e.g., phenyllithium, or of an albromide admixture, or in chloroform solution or minkali metal lower-alkoxide with a different lowereral oil suspension, indicate existence predominantly as alk l, Whil hi reaction i run f bl i h l structure ll and we have preferred to use the names er-alkanol as the solvent, it also can be carried out based on structure ll, although it is understood that eiusing a solvent inert under the reaction conditions, e.g., {her or both structures are comprehended. acetonitrile, dimethylformamide, tetrahydrofuran,

The intermediate compounds of Formula ll and/or ll ther, chloroform. benzene. toluene, and the like. are disclosed and claimed in said copending application The reaction which Comprises hydrolyzing under Ser. No. 144,307. acidic conditions lowcr-alkyl 4-(lower-alkoxy)-7(Q- The molecular structures of the composition aspects 4-pyridyl)-3-quinolinccarboxylate (I, Q is lowerof the invention were established by their mode of synalkoxy) to produce lower-alkyl l,4-dihydro-7-(O'-4- thesis and confirmed by the correspondence of calcupyridyl)-3-quinolinccarboxylate (II) is conveniently lated and found values for the elementary analyses and carried out by heating on a steam bath in an aqueous molecular weight determinations using the mass specacidic medium lower-alkyl 4-(lower-alkoxy)-7-(Q'-4- trograph for representative examples and by infrared, pyridyl)-3-quinolinecarboxylate. While aqueous nitric ultraviolet and NMR spectral analyses. acid is preferred in practicing our invention because of EXAMPLE 1 Ethyl 4-chloro-7 (4-pyridyl)-3-quinolinecarboxylate A mixture containing g. of ethyl 1,4-dihydro-4- oxo-7-(4-pyridyl)-3-quinolinecarboxylate and 100 ml. of phosphorus oxychloride was heated with stirring on a steam bath under anhydrous conditions for 40 minutes. The resulting solid-liquid reaction mixture was allowed to cool to room temperature and the solid collected. The solid was dissolved in 400 ml. of water. The aqueous solution was neutralized with ammonium hydroxide whereupon a solid precipitated. The solid was extracted from the aqueous mixture with chloroform. The chlorofrom extract was dried over anhydrous potassium carbonate and evaporated in vacuo to remove the chloroform. The residue was recrystallized from I00 ml. of ethanol to yield 5.90 g. of ethyl 4-chloro-7- (4-pyridyl)-3-quinolinecarboxylate, m.p. l33-l36C. Following the procedure described in Example 1 but using a molar equivalent quantity of phosphorus oxybromide in place of phosphorus oxyehloride, the product obtained is ethyl 4-bromo-7-(4-pyridyl)-3- quinolinecarboxylate.

Ethyl 4-chloro-7-(4-pyridyl)-3-quinolinecarboxylate also is obtained following the procedure described in Example 1 but using in place of phosphorus oxychloride a molar equivalent quantity of phosphorus trichloride, phosphorus pentachloride, thionyl chloride, phenylphosphonic dichloride or phosgene as the chlorinating agent.

EXAMPLE 2 Ethyl 4-ethoxy-7-(4-pyridyl)-3-quinolinecarboxylate An 8.4 g. portion of ethyl 4-chloro-7-(4-pyridyl)-3- quinolinecarboxylate was dissolved in 400 ml. of ethanolat about 35C. and to this solution was added with stirring 4.5 g. of sodium methoxide. Sodium chloride was observed to precipitate at once. The mixture was stirred at room temperature (about 25C.) for 10 minutes, refluxed for l0 minutes, cooled to room temperature and then neutralized with acetic acid. The resulting mixture was concentrated in vacuo at about 50C. The residue was triturated with chloroform, the insoluble materials removed by filtration and the filtrate concentrated in vacuo at about 50C. To the residual oily material was added 500 ml. of ether whereupon a solid precipitated. The solid was filtered off and the filtrate was evaporated to a volume of about 100 ml. and allowed to cool. The resulting crystalline precipitate was collected and dried to yield 3.8 g. of ethyl 4-ethoxy-7- (4-pyridyl)-3-quinolinecarboxylate, m.p. 100C. (immersed in l00 C. bath).

Following the procedure described in Example 2 but using methanol in place of ethanol. there is obtained methyl 4-methoxy-7-( 4-pyridyl )3- quinolinecarboxylate.

Following the procedure described in Example 2 but using in place of ethyl 4-chloro-7-(4 pyridyl)-3- quinolinecarboxylate and sodium methoxide respective molar equivalent quantities of ethyl 4-bromo-7-(4- ovridvll-3-quinolinecarboxvlate and Dotassium cthox- 6 ide, there is obtained ethyl 4-ethoxy=7-(4-pyridyl)-3- quinolinecarboxylate.

The following compounds are prepared by reacting ethyl 4-chloro-7-(4-pyridyl)-3-quinolinecarboxylate with the appropriate sodium, potassium or lithium lower-alkoxide using dimethylformamide as solvent, a reaction temperature of about 3'5-S0C., removal of the solvent in vacuo at about 50C., triturating the' residue with chloroform in Example 2, removal of the chloroform in vacuo. and treatment of the residue with ether as in Example '2 to yield a solid product: Ethyl 4- n-propoxy-7-(4-pyridyl)-3-quinolinccarlmxylate using lithium n-propoxide. ethyl 4-isopropoxy-7-(4-pyridyl)- 3-quinolinecarboxylate. using potassium isopropoxide. ethyl 4-n-butoxy-7-(4-pyridyl)-3-quinolinecarboxylate using sodium n-butoxide, ethyl 4-isobutoxy-7-(4- pyridyll-3-quinolinecarboxylate using potassium isobutoxide, ethyl 4-n-amoxy-7-(4-pyridyl)-3- quinolinecarboxylate using sodium n-amoxide or ethyl 4-n-hexoxy-7-(4-pyridylJ-3-quinolinecarboxylate using sodium n-hexoxide. V

Ethyl 4-ethoxy-7-(4-pyridyl)-3-quinolinecarboxylate also was isolated in yields of up to about 18% in the lstirred mixture kept at about 65 to 68C. was added dropwise over a period of about seventy-five minutes 84 g. of diethyl sulfate. The reaction mixture was heated with stirring for an additional one hour at the same temperature and then concentrated in vacuo. The residue was treated with water, the mixture stirred for about fifteen minutes and thenfiltered. The solid was washed with water and recrystallized from 700 ml. of isopropyl alcohol using decolorizing charcoal and dried at C. to yield g. of product; the isopropyl alcohol filtrate (21) containing the 4-ethoxy compound was saved and worked up as described hereinbelow. The l-ethylated final product was dissolved in chloroform; the chloroform solution was washed twice with water, dried over anhydrous potassium carbonate, treated with decolorizing charcoal, filtered and the chloroform removed in vacuo; the residue was crystallized from isopropyl alcohol, washed with isopropyl alcohol and n-pentane, and dried to yield 80 g. of ethyl l-ethyl-l ,4- dihydro-4-oxo-7-(4-pyridyl)-3-quinolinecarboxylate, m.p. l64-l 70C.; the isopropyl alcohol filtrate (d) was saved.

The filtrate (a) was concentrated in vacuo to remove the chloroform. The residue was dissolved in chloroform; water was added; and, the mixture was filtered. The layers were separated. The chloroform layer was washed twice with water, dried over anhydrous potassium carbonate, treated with decolorizing charcoal and filtered. The filtrate was concentrated in vacuo to remove the chloroform. The residue was recrystallized from ml. of isopropyl alcohol to yield 17 g. ofsolid,

which was combined with 8 g. of solid obtained by removing the solvent from the filtrate (d). A 19 g. portion of this combined solid was recrystallized from 300 ml. of isopropyl acetate to yield another 4.7 g. of the lethyl product. The isopropyl acetate filtrate was cooled in an ice bath for a few minutes. The resulting crystalline precipitate was collected and recrystallized from a small amount of isooroovl acetate using decolorizin charcoal to yield 5.0 g. of ethyl 4-ethoxy-7-(4-pyridyl 3-quinolinecarboxylate, m.p. 99100C. The structure of this compound was confirmed by its NMR and IR spectra.

EXAMPLE 3 Ethyl l,4-dihydro-4-oxo-7-( 4-pyridyl )-3- quinolinecarboxylate To a stirred suspension containing 270 g. of ethyl 4- ethoxy-7-(4-pyridyl)-3-quinolinecarboxylate and eight liters of warm water heated on a steam bath was added steamwise over a period of 15 minutes a solution containing 79 ml. of 90% nitric acid in 200 ml. of water. The initially formed nitrate salt was colloidal and stirring was rather slow. As the ethyl ether was hydrolyzed, the precipitate became more granular and after about ninety minutes a nicely powdered solid was formed. The resulting light green product was filtered; was washed successively with three 50 ml. portions of 5% nitric acid, three 150 ml. portions of isopropyl alcohol and three 50 ml. portions of ether; and then dried at 60C. in vacuo to yield 270 g. of ethyl l,4-dihydro-4- oxo-7-(4-pyridyl)-3-quinolinecarboxylate as its nitrate salt, m.p. 290C. A solution containing 400 g. of ammonium chloride in four liters of water was heated on a steam bath to 90C. and 200 g. of ethyl l,4-dihydro- 4-oxo-7-( 4-pyridyl)-3-quinolinecarboxylate nitrate was added in one portion. The suspension was stirred vigorously and l00 ml. of ammonium hydroxide was added dropwise over a period of minutes. A yellow mushy precipitate resulted and the mixture was stirred for an additional 50 minutes whereupon the precipitate be-' came more granular. The precipitate was collected and washed successively with three 50 ml. portions of 371 ammonium hydroxide and three'50 ml. portions of isopropyl alcohol. The product was then slurried in 400 ml. of acetone and the slurry filtered. The product was washed with four 200 ml. portions of ether and dried at 60C. in vacuo overnight (about 15 hours) to yield 225 g. of ethyl l,4-dihydro-4-oxo-7-(4-pyridyl)-3- quinolinecarboxylate, mp. 290C. with decomposition.

A 17 g. sample of ethyl 1,4-dihydro-4-oxo-7-(4- pyridyl)-3-quinolinecarboxylate nitrate was hydrolyzed with dilute sodium hydroxide solution at reflux to give after acidifying with acetic acid 12 g. of l,4-dihydro-4- oxo-7-(4-pyridyl)-3-quinolinecarboxylic acid, m.p. 300C.

Following the procedure described in Example 3 but using in place of ethyl 4-ethoxy-7-(4-pyridyl)-3- quinolinecarboxylate a molar equivalent quantity of methyl 4-methoxy-7-(4-pyridyl)-3- quinolinecarboxylate, ethyl 4-n-propoxy-7-(4-pyridyl)- 3-quinolinecarboxylate, ethyl 4-isopropoxy-7-(4- pyridyl)-3-quinolinecarboxylate, ethyl 4-n-butoxy-7- (4-pyridyl)-3-quinolinecarboxylate, ethyl 4-isohutoxy- 7-( 4-pyridyl )-3-quinolinecarboxylatev ethyl 4-namoxy-7-(4-pyridyl)-3-quinolinecarboxylate or ethyl 4-n-hexoxy-7-( 4-pyridyl )-3-quinolinecarboxylate. there is obtained methyl l,4-dihydro-4-oxo-7-(4- pyridyl)-3-quinolineearboxylate fromthe methyl 4- methoxy compound and there is obtained ethyl 1.4- dihydro-4-oxo-7-(4-pyridyl)-3-quinolineearboxylate from each of the remaining ethyl 4-(lower-alkoxy) compounds.

EXAMPLE 4 Ethyl 4-chloro-7-( 2,6-dimethyl-4-pyridyl )-3- quinolinecarboxylate is prepared following the procedure described in Example I using a molar equivalent quantity of ethyl l.4-dihydro-7-t2.6-dimetltyl-4- pyridyll-4-oxo-3-quinolinecarboxylate in place ofethyl l,4-dihydro'7-( 4-pyritlyl )-4-oxo-3- quinolinecarboxylate.

EXAMPLE 5 Ethyl 4-ethoxy-7-( 2,6-dimethyl-4-pyridyl l-3- quinolinecarboxylate. m.p. l46l48C., is prepared following the procedure described in Example 2 using ethyl 4-chloro-7-( 2,6-dimethyl-4-pyridyl )-3- quinolinecarboxylate, sodium methoxide and ethanol as the solvent.

Ethyl 4ethoxy-7-( 2,6-dimethyl-4-pyridyl l-3- quinolinecarboxylate also was isolated as a by-product in yields of up to about 35% in the l-ethylation of ethyl l,4-dihydro-7-( 2,6-dimethyl-4-pyridyl )-4-oxo-3 quinolinecarboxylate, for example, using diethyl sulfate as the ethylating agent, illustrated as follows: To 6.3 liters of dry dimethylformamide was added with stirring 425 g. of ethyl l,4-dihydro-7-(2,6-dimethyl-4-pyridyl)- 4-oxo-3-quinolinecarboxylate and 309 g. of anhydrous potassium carbonate. After 500 ml. of dimethylformamide had been distilled off in vacuo to ensure anhydrous reaction conditions, the reaction mixture was heated on a steam bath for about 40 minutes, cooled to C. and then treated dropwise over a period of about forty minutes, with stirring, with a solution containing 271 g. of diethyl sulfate in 100 ml. of dry dimethylformamide, keeping the reaction temperature between 7075C. After the addition had been completed, the reaction mixture was heated to 95C. and held there for 1 hour, cooled to 30C. and filtered. The filtrate was concentrated in vacuo to dryness. The solid was refluxed with six liters of n-heptane and filtered while hot. washing the solid with l.500 ml. of hot n-heptane. The combined n-heptane filtrate and washings which contained the 4-ethoxy by'product were saved and worked up as described hereinbelow. The solid final product, i.e., the l-ethylated compound, was dissolved in six liters of hot chloroform; the hot solution treated with decolorizing charcoal and filtered; and the filtrate concentrated in vacuo to remove the chloroform. The solid residue was recrystallized from ten liters of boiling isopropyl acetate using decolorizing charcoal and dried in vacuo at 60C. to yield 260 g. of ethyl l-ethyl l,4- dihydro-7-( 2,6-dimethyl-4-pyridyl )-4-oxo-3- quinolinecarboxylate, m.p. 168-l70C. Another 36 g. of the final product, m.p. l66-l 68C., was obtained by concentrating the mother liquor to one liter and collecting the precipitate.

The above-noted combined n-heptane filtrate and washings containing the o-ethylated compound was concentrated in vacuo to remove the n-heptane, thereby yielding 144 g. of ethyl 4-ethoxy-7-(2,6- dimethyl-4-pyridyl)-3-quinolinecarboxylate, m.p. l46-l48C.

EXAMPLE 6 Ethyl l.4-dihydro-7-( 2.6-dimethyl-4-pyridyl )-4-oxo-3- quinolinecarboxylate To a stirred suspension containing I92 g. of ethyl 4- ethoxy-7-( 2,6-dimethyl-4-pyridyl )-3- quinolinecarboxylate and 6 liters of water heated on a steam bath was added 52 ml. of 9071 nitric acid. The

reaction mixture was heated with stirring at C. for 90 minutes, cooled to 40C. and the precipitate eollected. 'l'his precipitate of ethyl l.4-dihydro-7-(2.6- tlimethyl-4-pyridyl)-4-oxo-3-quinolinecarboxylatc as its nitrate salt was slurried in water and excess ammonium hydroxide was added to liberate the free base form of said compound. The precipitate was collected, washed with water, slurried with 2 liters of acetone for about 3 hours and filtered, and then dried in vacuo at 60C. to yield 92 g. of ethyl l,4-dihydro-7-(2,6- dimethyl-4-pyridyl)-4-oxo-3-quinolinecarboxylate, mp. 205C. with decomposition.

EXAMPLE 7 Ethyl 4-chloro-7-(2'methyl-4-pyridyU-3- quinolinecarboxylate is prepared following the procedure described in Example 1 using in place of ethyl l,4- dihydro-4-oxo-7-(4-pyridyl)-3-quinolinecarboxylate a molar equivalent quantity of ethyl 1,4-dihydro-7-(2- methyl-4-pyridyl)-4-oxo-3-quinolinecarboxylate.

EXAMPLE 8 Ethyl 4-ethoxy-7-(2-methyl-4-pyridyl)-3- quinolinecarboxylate is prepared following the procedure described in Example 2 using in place of ethyl 4- chlor-7-(4-pyridyl)-3-quinolinecarboxylate a molar equivalent q y of ethyl y fimaae'seabaihemigre l but 'us'ihg in place of ethyl pyridyl)-3-quinolinecarboxylate.

EXAMPLE 9 Ethyl l.4-dihydro-7-(2-methyl-4-pyridyl)-4-oxo-3- quinolinecarboxylate is prepared following the procedure described in Example 3 but using in place of ethyl 4-ethoxy-7-(4-pyridyl)-3-quinolinecarboxylate a molar equivalent quantity of ethyl 4-ethoxy-7-(2-methyl-4- pyridyl)-3-quinolinecarboxylate.

EXAMPLE l0 Ethyl 4-chloro-7-(2.5-dimethyl-4-pyridyl)-3- quinolinecarboxylate is prepared following the procedure described in Example 1 using in place of ethyl l.4- dihydro-4-oxo-7-(4-pyridyl)-3-quinolinecarboxylate a molar equivalent quantity of l,4-dihydro-7-(2,5- dimethyl-4-pyridyl)-4-oxo-3-quinolinecarboxylate.

EXAMPLE ll Ethyl 4-ethoxy-7-(2,5-dimethyl-4-pyridyl)-3- quinolinecarboxylate is prepared following the procedure descrribed in Example 2 using in place of ethyl 4- chlorofl-(A-pyridyl)- 3-quinolinecarboxylate a molar Ethyl 4-chloro-7-(2,3-dimethyl-4-pyridyl)-3- quinolinecarboxylate is prepared following the procedure described in Example I using in place ol'cthyl 1.4-

dihydro-4-oxo-7-(4-pyridyl)-3-quinolincearlmxylatc a molar equivalent quantity of ethyl l,4-dihydro-7-( 2.3- dimethyl-4-pyridyl)-4-oxo-3-quinolineearboxylate.

EXAM PLE l4 Ethyl 4-ethoxy-7-( 2,3-dimethyl-4-pyridyl )-3- quinolinecarboxylate is prepared following the procedure described in Example 2 using in place of ethyl 4- chloro-7-(4-pyridylJ-Lquinolinecarboxylate a molar equivalent quantity of ethyl 4-chloro-7-(2,3-dimethyl- 4-pyridyl)-3-quinolinecarboxylate.

EXAMPLE l5 EXAMPLE l6 Ethyl 4-chloro-7-(2,6-diethyl-4-pyridyl)-3- quinolinecarboxylate is obtained following the procel,4-dihydro-4-oxo-7-(4-pyridyl )-3- quinolinecarboxylate a corresponding molar equivalent quantity of ethyl 7-(2.6-diethyl-4-pyridyl)-l.4-dihydro- 4-oxo-3-quinolinecarboxylate.

EXAMPLE I? Ethyl 4-ethoxy-7-(2,6-diethyl-4-pyridyl)-3- quinolinecarboxylate is obtained following the procedure described in Example 2 but using in place of ethyl 4-chloro-7-(4-pyridyl)J-quinolinecarboxylate a molar equivalent quantity of ethyl 4-chloro-7-(2.6-diethyl-4- pyridyl)-3-quinolinecarboxylate.

EXAMPLE l8 Ethyl 7-(2,6-diethyl-4-pyridyU-l,4-dihydro-4-oxo-3- quinolinecarboxylate is obtained following the procedure described in Example 3 using in place of ethyl 4- ethoxy-7-(4-pyridyl)-3-quinolinecarboxylate a molar equivalent quantity of ethyl 4-ethoxy-7-(2.6-diethyl-4- pyridyl)-3-quinolinecarboxylate.

We claim:

1. A compound of the formula where Q is halo, R is lower-alkyl and O is hydrogen or from one to two non-tertiary lower-alkyl groups.

2. Ethyl 4-chloro-7-(4-pyridyl)-3- quinolinecarboxylate according to claim I.

3. Ethyl 4-chloro-7-(2,6-dimethyl-4-pyridyl)-3- quinolinecarboxylate according to claim l.

* k l =l 

2. Ethyl 4-chloro-7-(4-pyridyl)-3-quinolinecarboxylate according to claim
 1. 3. Ethyl 4-chloro-7-(2,6-dimethyl-4-pyridyl)-3-quinolinecarboxylate according to claim
 1. 